Diseases of the myelin sheath are divided into two categories. The first category is the demyelinating or myelinoclastic diseases and the second is the dysmyelinating diseases. The myelinoclastic (demyelinating) diseases contain multiple sclerosis, myelinoclastic diffuse sclerosis, post-infectious and postvaccinal encephalomyelitis (disseminated vasculomyelinopathy), transverse myelitis, central pontine myelinolysis, and marchiafava-bignami disease.
The dysmyelinating diseases (leukodystrophies) contain metachromatic leukodystrophy, globoid cell leukodystrophy, adrenoleukodystrophy, andspongy sclerosis.
The first group (the demyelinating diseases) includes conditions in which the myelin sheath has developed normally and has a completely normal metabolic maintenance system, but in which the sheath appears to be the primary target of various conditions. In this group, two subgroups are recognized. The first one is multiple sclerosis, and some of its variants. The second group consists of the complications of various infections, principally viral, and vaccinations, which result from a misdirection of the immune response that has been activated by the infection or vaccination. Therefore, both humoral and cellular (delayed) Immune factors cause the myelin sheath of either the central or the peripheral nervous systems, or of both, to become inflammed, edematous, or destroyed.
In the second category, the dysmyelinating diseases, an inborn error of metabolism causes a disturbance of myelinogenesis. The dysmyelination may result from a metabolic failure of the myelin maintenance system after normally formed myelin has been laid down.
The dysmyelinating diseases are of many types and include such disparate conditions as the leukodystrophies the gangliosidoses, such as Tay-Sachs disease; several amino-acidopathies, such as phenylketonuria and maple syrup urine disease; and probably other metabolic disturbances which in one way or another interfere with the normal development of myelin.
It should be pointed out that destruction of myelin is a nonspecific result of almost any injury to the nervous system and can be seen following physical trauma or vascular insults, with infections and neoplasms, or as a result of various intoxications. The conditions considered here are those in which such causes and factors are not recognized. Two conditions, central pontine myelinolysis and Marchiafava-Bignami disease, have been included because they fulfill the criteria of being primary diseases of myelin, although they are not easily classifiable as either variants of multiple sclerosis or instances of postinfectious or postvaccinal reactions of the nervous system.
The conditions to be described here affect primarily, but not exclusively, the central nervous system. While multiple sclerosis is a disease restricted to the central nervous system, the leukodystrophies normally also involve the peripheral nerves; the postinfectious or postvaccinal reactions may be restricted to the central nervous system (encephalomyelitis), or peripheral nervous system (Guillain-Barre syndrome) or may involve both to varying degrees.
In the experimental allergic encephalomyelitis (EAE) animal model. administration of myelin basic protein (MBP) induces EAE (Higgins et al., J. Immunol., 140(2), 440-445, Jan. 15, 1988; Bitar et al., Cell. Immun., 112, 364-370, (1988), and is characterized by increased levels of TGF.beta. and IL-5 in the brain (Khoury et al., J. Exp. Med., 176, 1355-1364, November 1992). Agents which induce TGF.beta.and other antiinflammatory cytokine(s) may be useful for the described diseases and their symptoms.